Abstract
BACKGROUND: Solid tumors often develop hypoxic regions, leading to aggressive behavior and increased drug resistance. METHODS: The chemical composition of Cymbopogon citratus essential oil (EO) was analyzed using GC-MS. Alginate nanoparticles containing the EO and its primary component, citral, were synthesized via the ionic gelation method. Encapsulation was confirmed using ATR-FTIR analysis. The anticancer efficacy of C. citratus EO, citral, and their respective alginate nanoparticles was evaluated under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions on breast cancer (MDA-MB-231) and melanoma (A-375) cell lines. Additionally, qPCR and flow cytometry were used to assess apoptosis gene expression ratios (Bax/Bcl-2) and levels of apoptosis. RESULTS: Citral (80.98%) was identified as the major component of the EO. Alginate nanoparticles containing C. citratus EO and citral (C. citratus-AlgNPs and citral-AlgNPs) were synthesized with particle sizes of 195 ± 4 nm and 222 ± 9 nm, and zeta potentials of -22 ± 3 mV and - 17 ± 1 mV, respectively. Both samples demonstrated significantly greater efficacy under hypoxic conditions. Citral and C. citratus-AlgNPs had IC(50) values of 27 (19-39) µg/mL and 25 (4-147) µg/mL, respectively, against MDA-MB-231 and A-375 cells. Flow cytometry showed increased apoptosis under hypoxic conditions, with the highest rates observed for citral-AlgNPs and C. citratus-AlgNPs (84 ± 5 and 92 ± 5% in MDA-MB-231 and A-375 cells, respectively). CONCLUSION: This study demonstrates that alginate nanoparticles enhance the anticancer activity of C. citratus-AlgNPs and citral, particularly under hypoxic conditions, highlighting their potential for hypoxia-targeted cancer therapies.